The cell cycle inhibitor flavopiridol was previously shown in animal models to improve SCI recovery. However, the systematic dosage of flavopiridol is with side effects and the mechanism is not clear. This study aims to develop a strategy for local delivery of flavopiridol and investigate its mechanisms of function as well. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) was used for the sustained delivery of flavopiridol. The spinal cords were right-hemisectioned and NPs were administered into the injury site. Transparent spinal cord technology was applied for the three-dimensional observation of the anterograde tracing. The results showed that flavopiridol NPs had a susteined release of up to 3 days in vitro. Flavopiridol NPs significantly decreased inflammatory factor synthesis of astrocytes, including tnf-alpha, il-1beta, and il-6, while the il-10 expression was elevated. In-vivo study demonstrated that flavopiridol NPs decreased inflammatory expression and glial scarring, and facilitated neuronal survival and neural transmitting. Cavitation volume was decreased by proximately 90%. Administration of flavopiridol NPs also improved the motor recovery of injured animals. These findings illustrated that local delivery of flavopiridol in PLGA NPs improved SCI recovery through inhibiting astrocyte growth and inflammatory factor synthesis.
2014-05-02
NSFC grants （81330041）
Center for Stem Cell and Tissue Engineering, School of Medicine, Zhejiang University
2011-03-25
CQ算法求解分离可行性问题，仅涉及到分别向C、Q上的正交投影，这使它成为求解SFP的一个最重要的方法，但是参数γ的影响不是很清楚。这篇文章的目的是研究随着参数γ的变化怎样影响收敛时间，获得了一些结果。在文章的最后给出了一些数值试验。
Based on the very recent work by A Moudafi (2010 Inverse Problems 26 055007 (6pp)), Censor and Segal (2009 J. Convex Anal.16 587-600) and Xu's results. We extend their algorithms of demicontractive operators to the class of pseudo-demicontractive operators for the split common fixed-point problem in a Hilbert space and give the strong convergence theorem. Our results improve and/or develop Moudafi and Censor's results.
2011-04-02
This research was supported partly by NSFC Grants（No:11071279）
Department of Mathematics, Tianjin Polytechnic University,Department of Mathematics,Tianjin Polytechnic University
Objective: Stromal interacting molecule 1 (STIM1) is associated with neointima hyperplasia by mediating store-operated Ca2+ entry (SOCE) in multiple cell types. We tested whether the small molecule SOCE inhibitor could prevent neointima formation and vascular stenosis using 2-aminoethyl diphenylborate (2-APB) as a prototype drug. Methods: VSMCs were isolated from rat aortas or rabbit common carotid arteries using the tissue explant protocol and phenotypic modulation was induced by 5% fetal bovine serum (FBS). VSMC proliferation was determined using the propidium iodine/ bromodeoxyuridine double-staining method. Neointimal hyperplasia was induced in rabbit carotid arteries by air-drying injury, and 2-APB was dissolved in PLF-127 gel and coated to the extravascular surface with rapamycin as a vis-à-vis control. Results: SOCE in the VSMCs was inhibited by 2-APB accompanied by cell cycle arrest in the G1 phase. In air drying-induced rabbit carotid artery injury models, extravascular application of 2-APB effectively blunted neointima formation with a potency comparable to rapamycin. 2-APB also attenuated leukocyte infiltration by perturbing the degranulation process preserving integrity of the internal and external elastic lamina. Likewise, the SOCE inhibitor prevented platelet activation but very likely in part by an indirect mechanism involving leukocyte inactivation. More interestingly, 2-APB did not seem to induce thrombosis, a fetal complication of public concern with the use of sirolimus-eluting stents. Conclusion: Small molecule SOCE inhibitors like 2-APB could blunt neointima hyperplasia without inducing thrombosis, and thus may serve as potentially new therapeutic agents for the prevention of restenosis and proliferative vascular disorders including hypertension, coronary heart disease and diabetes. (Corresponding authors: stang@ nankai.edu.cn or stellarli@ nankai .edu.cn)
2012-02-15
MOE Doctorial Training Funds （200800550036）
NSFC grants （30871011 and 81072629）
Tianjin Science and Technology Support Project （08ZCKFSH04500）
Tianjin Natural Science Foundation （10JCYBJC14800）
Project “973” grant（2010CB945001）
Department of Pharmacology, Nankai University School of Medicine, TianJin 300071, Department of Medicine, Tianjin Chest Hospital, Tianjin 300071,Department of Pharmacology, Nankai University School of Medicine, Tianjin 300071,Department of Pharmacology, Nankai University School of Medicine, Tianjin 300071,Department of Pharmacology, Nankai University School of Medicine, Tianjin 300071,Department of Pharmacology, Nankai University School of Medicine, Tianjin 300071,Department of Biochemistry and Cardiovascular Research Center,Philadelphia, PA 19104, USA,Department of Biochemistry and Molecular Biology, Libin Cardiovascular Institute of Alberta, The University of Calgary, Alberta, Canada T2N 4N1,Department of Biochemistry and Cardiovascular Research Center,Philadelphia, PA 19104, USA
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